The aims of this study are to evaluate the relative contributions of atrial stretch receptors and atrial natriuretic peptides to the increases in sodium excretion and urine flow that occur in response to stimuli that elevate left atrial pressure. Another aim is to establish a dose-response relationship between a-human atrial natriuretic peptide (ahANP) and a large number of renal and cardiovascular variables. Finally, we propose to determine whether neuropeptide-Y (NPY) is released from the atrial when they are distended and, if so, to determine whether a combined infusion of ahANP and NPY acts synergistically to augment renal salt and water excretion. Because left atrial distension also elicits cardiovascular changes, we will monitor multiple hemodynamic variables and analyze them as part of each series of experiments. These studies are health related because it is clear that the concentration of ANP in plasma is altered in both acute and chronic cardiovascular disease. There are reasons to suspect that the concentration of NPY in plasma also may be altered under similar conditions. In addition, atrial stretch receptors are distorted by chronic elevations of atrial pressure and reportedly become less responsive to stretch. Because these components of the atrial appear to be involved directly in the regulation of fluid balance and a number of cardiovascular variables, certain abnormalities in fluid balance that commonly occur in patients with cardiovascular disease may be attributable, at least in part, to adverse effects arising from one or more of the atrial components described above. A better understanding of the physiological and pathophysiological mechanisms influencing salt and water balance should offer clues to better management of patients with derangements in body fluid balance.